Silencing IKBKE inhibits the migration and invasion of glioblastoma by promoting Snail1 degradation
Clin. transl. oncol. (Print)
; 24(5): 816-828, mayo 2022.
Artigo
em Inglês
| IBECS
| ID: ibc-203784
Biblioteca responsável:
ES1.1
Localização: ES15.1 - BNCS
ABSTRACT
PurposeGlioblastoma multiforme (GBM) is one of the most common malignant brain tumors in adults and has high mortality and relapse rates. Over the past few years, great advances have been made in the diagnosis and treatment of GBM, but unfortunately, the five-year overall survival rate of GBM patients is approximately 5.1%. Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE) is a major oncogenic protein in tumors and can promote evil development of GBM. Snail1, a key inducer of the epithelial-mesenchymal transition (EMT) transcription factor, is subjected to ubiquitination and degradation, but the mechanism by which Snail1 is stabilized in tumors remains unclear. Our study aimed to investigate the mechanism of IKBKE regulating Snail1 in GBM.MethodsFirst, we analyzed the correlation between the expression of IKBKE and the tumor grade and prognosis through public databases and laboratory specimen libraries. Second, immunohistochemistry (IHC) and western blot were used to detect the correlation between IKBKE and Snail expression in glioma samples and cell lines. Western blot and immunofluorescence (IF) experiments were used to detect the quality and distribution of IKBKE and Snail1 proteins. Third, In situ animal model of intracranial glioma to detect the regulatory effect of IKBKE on intracranial tumors.ResultsIn this study, Our study reveals a new connection between IKBKE and Snail1, where IKBKE can directly bind to Snail1, translocate Snail1 into the nucleus from the cytoplasm. Downregulation of IKBKE results in Snail1 destabilization and impairs the tumor cell migration and invasion capabilities.ConclusionOur studies suggest that the IKBKE-Snail1 axis may serve as a potential therapeutic target for GBM treatment.
Texto completo:
Disponível
Coleções:
Bases de dados nacionais
/
Espanha
Base de dados:
IBECS
Assunto principal:
Neoplasias Encefálicas
/
Regulação Neoplásica da Expressão Gênica
/
Movimento Celular
/
Glioblastoma
/
Linhagem Celular Tumoral
/
Transição Epitelial-Mesenquimal
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
Clin. transl. oncol. (Print)
Ano de publicação:
2022
Tipo de documento:
Artigo
Instituição/País de afiliação:
Cerebrovascular Disease Hospital/China
/
Ningbo Hospital of Zhejiang University/China
/
The Second Affiliated Hospital of Soochow University/China
/
Tianjin Medical University Cancer Institute and Hospital/China
/
Tianjin Medical University General Hospital/China
/
Zhengzhou University Peoples Hospital/China